Investigation of Mifepristone (RU486) on Stress Sensitivity and Relapse Prevention in Cocaine Dependent Patients

Investigation of the Effects of Mifepristone (RU486) on Stress Sensitivity and Relapse Prevention in Cocaine Dependent Patients

This research will evaluate the impact of blocking central and peripheral glucocorticoid receptors on stress sensitivity and the risk of relapse to cocaine use in treatment-seeking cocaine-dependent individuals. Mifepristone (RU-486) will be the glucocorticoid antagonist used.

Study Overview

• Status: Completed
• Conditions: Cocaine Dependence
• Intervention / Treatment: Drug: placebo; Drug: Mifepristone

Detailed Description

This study attempts to reduce relapse risk by blocking glucocorticoid receptors, and thus allow some of the changes in the brain caused by cocaine to redress themselves

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • STARS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Age 18 to 60.
2. Male.
3. Meets DSM?IV criteria for current cocaine dependence and is seeking treatment.
4. Identifies life stress (work, interpersonal, financial, etc) as a trigger for cocaine use or reports uncontrollable craving to use of cocaine.
5. Displays at least one cocaine-positive urine toxicology during screening.
6. Uses cocaine at least 4/30 days in the past month, or reports episodic binges of large amounts of cocaine (at least $200) at least 2x/month.
7. Able to give informed consent and comply with study procedures.

Exclusion Criteria:

1. Meets DSM-IV criteria for major depression, bipolar disorder, schizophrenia or any psychotic disorder other than transient psychosis due to drug abuse. Substance Induced Mood Disorder with Hamilton Depression Scale score ³13 will be excluded.
2. History of seizures in the last 2 years, or history of seizures related to the substance (cocaine, alcohol, or benzodiazepine) that the patient continues to use.
3. History of allergic, dermatological, or adverse event to mifepristone
4. Chronic organic mental disorder, insufficient proficiency in English that would render an individual incapable of giving informed consent.
5. Significant current suicidal risks, history of significant suicidal behavior or any suicide attempt within the past year.
6. Unstable physical disorders, which might make participation hazardous such as hypertension (>140/90), WBC < 3.5, new diagnosis of hepatitis (patients with chronic mildly elevated transaminase levels (£2-3 X upper limit of normal will be considered acceptable if PT/PTT is normal), renal failure (creat > 2; BUN > 40), or diabetes (HbA1c > 7%), and low Hb (< 12g/dL) or low Hct (<36%).
7. Coronary vascular disease as indicated by history, or suspected by abnormal ECG or history of cardiac symptoms. Hx of cardiac symptoms (chest pain, chest pressure, shortness of breath, syncope) during cocaine use.
8. Cardiac conduction system disease as indicated by QRS duration of ³ 0.11 msec.
9. Currently meets DSM-IV criteria for another substance dependence or abuse disorder other than nicotine, alcohol, or cannabis. If alcohol dependent, must not be in need of detoxification. Heavy male drinkers (who consume greater than 5 standard alcoholic drink per day per NIAAA definition) will be excluded.
10. Presents with metabolic indicators of hypoadrenalism such as low serum sodium (<130 mEq/L), high serum potassium (>5.5 mEq/L), Na/K ratio < 30:1, low fasting blood sugar (<50 mg/dL), or high BUN (>20 mg/dL), or a previous history of Addison's disease or adrenal insufficiency, or the presence of low K (< 3.5 mEq/L). spot AM cortisol <5ug/dL, PM cortisol < 3 ug/dL
11. Participants who cannot comply with study procedures during the initial hospitalization phase.
12. Supplemental exclusion criteria for cold pressor test (CPT): history of frostbite, open cut or sore on foot to be immersed, history of Raynaud's phenomenon. During the testing, if sBP > 190 or dBP > 120, or HR > 160, the test will be interrupted. A second occurrence of these values will stop all further CPT.

13: Patients taking medications metabolized by cytochrome 3A4 (ex: erythromycin, protease inhibitors) or that inhibit this cytochrome; or consuming grapefruit juice.

14: Patients with an underlying hemorrhagic disorder and those on anti-coagulants. INR > 1.1, PT > 17 msecs, total plt <100x109/L.

15: Use of treatment agents that inhibit steroid biosynthesis by the adrenal cortex, such as metyrapone, ketoconazole, fluconazole, aminoglutethimide, or etomidate. Patients also requiring inhaled steroids.

16. Female

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo; Placebo	Drug: placebo; placebo
Active Comparator: Mifepristone; Mifepristone 600mg	Drug: Mifepristone; Mifepristone 600mg, 3x/wk for 4 weeks; Other Names: RU486

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Relapse by Days 10 and 28	assessed percent of sample with documented cocaine use by days 10 and 28 based on self reported use and urine toxicology. Those with documented use were considered to have relapsed.	assessed during 8 weeks of trial, but reported for days 10 and 28 of trial

Collaborators and Investigators

• Sponsor: New York State Psychiatric Institute
• Investigators: Principal Investigator: Wilfid N Raby, Md, PhD, NYSPI

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): February 14, 2018

Study Registration Dates

• First Submitted: May 26, 2010
• First Submitted That Met QC Criteria: May 28, 2010
• First Posted (Estimate): May 31, 2010

Study Record Updates

• Last Update Posted (Actual): December 20, 2018
• Last Update Submitted That Met QC Criteria: November 27, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Cocaine Dependence
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Cocaine-Related Disorders; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Abortifacient Agents; Luteolytic Agents; Abortifacient Agents, Steroidal; Contraceptives, Postcoital, Synthetic; Contraceptives, Postcoital; Menstruation-Inducing Agents; Mifepristone
• Other Study ID Numbers: 6013; RU486 for Cocaine Dependence (Other Grant/Funding Number: NIDA K23 DA027044-01)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Data has been presented as an oral presentation at the annual meeting of the College on Drug Dependence in Palm Springs California on June 16th 2016. The data is presently being prepared for publication in a peer-reviewed publication.
• IPD Sharing Time Frame: the data will be available by the end of 2018, and will be indefinitely
• IPD Sharing Access Criteria: there will be no access criteria required
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code